Sadeeq Ullah

Molecular mechanism of tobramycin with human serum albumin for probing binding interactions: multi-spectroscopic and computational approaches

Binding interactions between human serum albumin (HSA) and tobramycin (TOB) under simulated physiological conditions (pH = 7.4) were explored using ultraviolet-visible absorption (UV), Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and fluorescence, as well as by computational modeling. Fluorescence quenching of HSA upon TOB addition was found to be a static quenching process, as revealed from the diminishing trend of the Stern–Volmer quenching constant with increasing temperature as well as UV-vis absorption spectral results. Fluorescence quenching value as titration results demonstrated an excellent binding affinity with binding constant Ks (2.06 × 106 M−1) between TOB and HSA. The FTIR and the CD spectra showed secondary and tertiary structural changes in the HSA, whereas three-dimensional fluorescence spectral results disclosed microenvironmental perturbations around aromatic fluorophores upon TOB binding. Competitive site-marker displacement results along with molecular modeling suggested the preferred location of the TOB binding site to be site I, located in subdomain IIA of HSA. The solvent accessible surface area (ASAs) calculations for the native HSA and HSA–TOB displayed a reduction in ASAs, providing strong support for effectiveness of TOB binding to HSA. These findings provide a useful experimental strategy for drug designers to further study the molecular binding mechanisms of TOB to HSA to gain better therapeutic efficacy.

Bio-fabrication of catalytic platinum nanoparticles and their in vitro efficacy against lungs cancer cells line (A549)

Platinum based drugs are considered as effective agents against various types of carcinoma; however, the severe toxicity associated with the chemically prepared platinum complexes limit their practical applications. Similarly, water pollution caused by various organic moieties is another serious health problem worldwide. Hence, an intense need exists to develop new, effective and biocompatible materials with catalytic and biomedical applications. In the present contribution, we prepared platinum nanoparticles (PtNPs) by a green route using phytochemicals as a source of reducing and stabilizing agents. Well dispersed and crystalline PtNPs of spherical shapes were prepared and characterized. The bio-fabricated PtNPs were used as catalyst and anticancer agents. Catalytic performance of the PtNPs showed that 84% of the methylene blue can be reduced in 32min under visible light irradiation (K=0.078min-1). Similarly the catalytic conversion of 4-nitrophenol to 4-aminophenol was achieved in <20min (K=0.124min-1). The in vitro anticancer study revealed that biogenic PtNPs are the efficient nano-agents possessing strong anticancer activity against the lungs cancer cells line (A549). Interestingly, the as prepared PtNPs were well tolerated by normal human cells, and therefore, could be effective and biocompatible agents in the treatment of different cancer cells.

Tobramycin mediated silver nanospheres/graphene oxide composite for synergistic therapy of bacterial infection

Graphene-based materials have attracted a significant attention in constructing hybrid systems for drug delivery with enhanced antimicrobial activities. In our work, we demonstrated the formation of silver nanoparticles (AgNPs) on graphene oxide (GO) using tobramycin (TOB), an aminoglycoside antibiotic, as reducing and decorating agent. The TOB decorated GO AgNPs (TOB-GO-Ag) composite was used as an antibacterial agent against multi-drug resistant Gram-negative E-coli (BL21 DE3). The reversal of surface potential from -30 mV (GO) to +20 mV confirms the successful reduction of GO by TOB. Atomic force microscopy (AFM) and high-resolution transmission electron microscopic (HRTEM) analyses confirmed the formation of uniformly distributed AgNPs on the reduced GO with an approximate particle size of 5 nm. The as-synthesized nanocomposite displayed significant antibacterial activity as compared to pure AgNPs and TOB. The positively charged TOB-GO-Ag interacts with the negatively charged E. coli membrane and inhibit bacterial growth by the antibacterial actions of the released silver, GO and tobramycin from the TOB-GO-Ag composite. The significant loss of bacterial membrane potential from -52 ± 2 mV (control) to -2 ± 1 mV (treated) indicates a severe cell wall damage caused by TOB-GO-Ag composite. Furthermore, fluorescence study also demonstrated a severe membrane disruption in bacterial cells treated with TOB-GO-Ag composite as compared to pure AgNPs and GO. In conclusion, the development of such hybrid systems would help in enhancing the efficacy of available drugs and eradicating the emerging bacterial resistance.

Palladium nanoparticles synthesis, characterization using glucosamine as the reductant and stabilizing agent to explore their antibacterial & catalytic applications

Low cost and an easy technique for the synthesis of palladium nanoparticles (PdNPs) was developed. Glucosamine was used to stabilize palladium precursor (PdCl2) into palladium nanoparticles. Several analytical techniques were used for the determination of morphology, crystalline structure; size, capping, and composition of synthesize palladium nanoparticles. The UV-visible spectroscopy SPR peak (Surface Plasmon Resonance) at 284 nm revealed synthesis of PdNPs. Energy dispersive X-ray (EDX) and X-ray diffraction (XRD) studies proved the elemental composition and crystalline structure of the synthesized palladium nanoparticles respectively. The average particle sizes (5.5 nm) were obtained by using the 1 M glucosamine solution, with a fixed amount of PdCl2 (4 mM). Moreover, the as synthesized PdNPs was evaluated against Gram negative bacterial E. which shows tremendous antibacterial activity as compare to tobramycin standard antibiotics. Its mechanistically found that PdNPs damage cell membrane and caused imbalance of metabolism system of the cell as a result production of reactive oxygen species (ROS). Thus, these finding revealed that cells become leaky and all organelles come out from cells, finally caused death of the E. coli. Addition, the as prepared PdNPs also showed excellent catalytic activities toward reduction of methylene blue and 4-nitrophenol.Thus, glucosamine mediated PdNPs having dual functions biomedical as well as intoxicating catalyst for industries.

Biogenic synthesis of silver nanoparticles using extracts of Leptolyngbya JSC-1 that induce apoptosis in HeLa cell line and exterminate pathogenic bacteria

Abstract Utilizing novel approaches for the green synthesis of metal nanoparticles are of great importance. Therefore, we reported biogenic synthesis of silver nanoparticles (AgNPs) using extracts of Leptolyngbya strain JSC-1, and their significant applications against pathogenic bacteria and cancerous HeLa cell line. The biofabricated AgNPs were characterized by UV–visible spectroscopy, FTIR, SEM, TEM, DLS and zeta-potential. The as prepared AgNPs were assessed for inhibition of bacterial growth and induction of apoptosis in HeLa cells by different doses of AgNPs was evaluated. UV–visible spectroscopy and FTIR of AgNPs demonstrated the surface plasmon resonance at 413 nm and interaction among extract and nanoparticles, respectively. Electron microscopy revealed the morphology and DLS demonstrated size distribution of the particles (10–100 nm). Zeta potential values were between −47 and 0 mV, indicating stability of the particles. Proliferation of HeLa cells was significantly inhibited and severe cytotoxicity with higher intracellular uptake were observed after applying high concentration of AgNPs. Efficient inhibition zones (17 ± 2 and 21 ± 2 mm) were produced at maximum concentration (100 µl from 1 mg ml−1 stock of AgNPs) for Staphylococcus aureus and Escherichia coli, respectively. These findings reveal that the biofabricated AgNPs possess strong antibacterial activity and ability to induce apoptosis in cancer cell line (HeLa).